Abstract Photothermal therapy (PTT) has been extensively explored as a promising alternative therapeutic approach for many malignant tumors. However, PTT agents never repair bone defects because of their lack of osteogenic activity. Therefore, the integration of multi-modal therapies into one platform could show great promise in overcoming the drawbacks of conventional single-modal therapy and achieving improved therapeutic efficacy in cancer. In this study, an indocyanine green (ICG) and diethylenetriamine/nitric oxide adduct (DETA/NO)-loaded polylactic acid (PLA) (PLIN) monolith was created via simple thermally induced phase separation (TIPS) and used to enhance PTT efficacy by killing residual cancer cells and regenerating bone defects after surgical resection of tumor tissues. The resulting PLIN monolith exhibited interconnected microporous structures and uniform morphology composed of leaf-like small units. The results of in vitro PTT efficacy tests demonstrated that the PLIN monolith exhibited enhanced photothermal activity on osteosarcomas but did not caused phototoxicity in normal osteoblasts. The synergistic cancer therapy efficacy of PLIN was mainly caused by high local temperature and elevated intracellular generation of ONOO− in MG63 cells. In addition, PLIN induced significant apoptotic cell death following laser irradiation. Therefore, the PLIN monolith has potential for application in osteosarcoma therapy and bone regeneration.

中文翻译：

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一氧化氮和活性氧释放聚乳酸整料用于增强骨肉瘤的光热治疗

摘要 光热疗法 (PTT) 已被广泛探索为许多恶性肿瘤的一种有前途的替代治疗方法。然而，PTT 剂从未修复骨缺损，因为它们缺乏成骨活性。因此，将多模式治疗整合到一个平台中，有望克服传统单模式治疗的弊端，提高癌症治疗效果。在这项研究中，通过简单的热致相分离 (TIPS) 创建了吲哚菁绿 (ICG) 和二亚乙基三胺/一氧化氮加合物 (DETA/NO) 负载的聚乳酸 (PLA) (PLIN) 整料，并用于通过以下方式提高 PTT 功效在手术切除肿瘤组织后杀死残留的癌细胞和再生骨缺损。由此产生的 PLIN 整体表现出相互连接的微孔结构和由叶状小单元组成的均匀形态。体外 PTT 功效测试的结果表明，PLIN 整料对骨肉瘤表现出增强的光热活性，但不会对正常成骨细胞造成光毒性。PLIN 的协同癌症治疗功效主要是由局部高温和 MG63 细胞中 ONOO− 的细胞内生成增加引起的。此外，PLIN 在激光照射后诱导显着的细胞凋亡。因此，PLIN 整体块在骨肉瘤治疗和骨再生中具有应用潜力。体外 PTT 功效测试的结果表明，PLIN 整料对骨肉瘤表现出增强的光热活性，但不会对正常成骨细胞造成光毒性。PLIN 的协同癌症治疗功效主要是由局部高温和 MG63 细胞中 ONOO− 的细胞内生成增加引起的。此外，PLIN 在激光照射后诱导显着的细胞凋亡。因此，PLIN 整体块在骨肉瘤治疗和骨再生中具有应用潜力。体外 PTT 功效测试的结果表明，PLIN 整料对骨肉瘤表现出增强的光热活性，但不会对正常成骨细胞造成光毒性。PLIN 的协同癌症治疗功效主要是由局部高温和 MG63 细胞中 ONOO− 的细胞内生成增加引起的。此外，PLIN 在激光照射后诱导显着的细胞凋亡。因此，PLIN 整体块在骨肉瘤治疗和骨再生中具有应用潜力。